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clostridium novyi-nt in cancer therapy

Genes & Diseases 2016年第2期3卷 144-152页

作者： Verena Staedtke Nicholas J.Roberts Ren-Yuan Bai Shibin Zhou Ludwig Center for Cancer Genetics and Therapeutics The Johns Hopkins Sidney Kimmel Cancer CenterBaltimoreMD 21287USA Department of Neurology The Johns Hopkins Medical InstitutesBaltimoreMD 21231USA Department of Pathology Sol Goldman Pancreatic Cancer Research CenterJohns Hopkins Medical InstitutionsBaltimoreMD 21231USA Department of Neurosurgery The Johns Hopkins Medical InstitutesBaltimoreMD 21231USA

The attenuated anaerobic bacterium clostridium novyi-nt(***-nt)is known for its ability to precisely germinate in and eradicate treatment-resistant hypoxic tumors in various experimental animal models and spontaneously occurring canine *** this article,we review the therapeutic and toxicologic aspects of ***-nt therapy,key challenges and limitations,and promising strategies to optimize its performance via recombinant DNA technology and immunotherapeutic approaches,to establish ***-nt as an essential tool in cancer therapy.

关键词： Bacteria Bacterial cancer therapy Cancer clostridium clostridium novyi-nt Hypoxia Immunotherapy

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Bacteriolytic therapy of experimental pancreatic carcinoma

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World Journal of Gastroenterology 2010年第28期16卷 3546-3552页

作者： Claudia Maletzki Michael Gock Ulrike Klier Ernst Klar Michael Linnebacher Department of General VascularThoracic and Transplantation SurgerySection of Molecular Oncology and ImmunotherapyUniversity of Rostock18057 RostockGermany

AIM:To investigate the effectiveness of clostridium novyi(***)-nt spores for the treatment of established subcutaneous pancreatic tumor in the syngeneic,immunocompetent Panc02/C57Bl/6 model. METHODS:***-nt spores were applied intravenously to animals carrying established pancreatic tumors of three different *** immune responses in peripheral blood and spleen were examined by flow ***,cytotoxic activity of lymphocytes against syngeneic tumor targets was analyzed. RESULTS:Application of spores identified,that(1) small tumors(450 mm3)responded with substantial necrosis followed by shrinkage and significant lethality most likely due to tumor lysis syndrome (n=6);and(3)an optimal treatment window exists for tumors of approximately 250 mm 3 (n=21).In this latter group,all tumor-bearing animals had complete tu-mor regression and remained free of tumor recurrence. In subsequent tumor rechallenge experiments a significant delay in tumor growth compared to the initial tumor cell inoculation was observed(tumor volume at day 28:197.8±87.3 mm 3 vs 500.1±50.9 mm3,Pntly mediated by the innate arm of the immune system. CONCLUSION:The observed complete tumor regression is encouraging and shows that immunotherapy with ***-nt is an interesting strategy for the treatment of pancreatic carcinomas of defined sizes.

关键词： Bacteriolytic immunotherapy clostridium novyi-nt Immune response Pancreatic carcinoma

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